The priority aim of the present work is to identify physical- biochemical properties other than those presently known to explain how and why cholesterol crystallization occurs in supersaturated bile. I. Cholesterol precipitation- two new measurement methods will be developed to observe specific properties of the solubility system: a) metastability limit - an index of the lowest state of supersaturation at which crystal growth is initiated and, b) rate of crystal growth - using these two indices, a clear physical-chemical separation of normal and "lithogenic" bile should become possible and most importantly these tests can be used as screens for chemical compounds having the desired capability of modifying "lithogenic" bile. II. Role of biliary mesophase in cholesterol microcrystal formation. Query: Does biliary mesophase retard crystallite nucleation? III. Liquid crystalline mesophase in human and diet-induced canine cholesterolosis. Query: How does this lipid deposition process relate to biliary lipids? Methods will include disappearance curve observations of cholesterol from appropriate metastably supersaturated solutions. Mesophase observations will include ultracentrifugal separation and characterization by the following techniques: chemical compositional analysis, light and transmission electron microscopy, short and wide angle x-ray diffraction. Among other screening techniques for testing efficacy of potential chemotherapeutic compounds described under I-b will be the further development of a previously unexplored in vivo animal model herein described which will provide a rapid, direct, safe and comparatively inexpensive tool for this purpose. Special emphasis will be placed on testing newly synthesized compounds as outlined in supplement A.